Isatoic Anhydride → 7-bromo-3-methyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361407노트

반응식

HRID 2361407 반응식
[NH2:1][C:2]1[C:3]([CH3:26])=[C:4]([C:8]2[C:20]3[C:19]4[C:14](=[CH:15][C:16]([Br:21])=[CH:17][CH:18]=4)[NH:13][C:12]=3[C:11]([C:22]([NH2:24])=[O:23])=[N:10][C:9]=2[CH3:25])[CH:5]=[CH:6][CH:7]=1.[NH:27]1[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[C:30](=O)[O:29][C:28]1=O.[N+](O[La](O[N+]([O-])=O)O[N+]([O-])=O)([O-])=O.COC(OC)OC>O1CCCC1.C(OCC)(=O)C>[Br:21][C:16]1[CH:15]=[C:14]2[C:19]([C:20]3[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([N:1]5[C:30](=[O:29])[C:31]6[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=6)[N:27]=[CH:28]5)[C:3]=4[CH3:26])=[C:9]([CH3:25])[N:10]=[C:11]([C:22]([NH2:24])=[O:23])[C:12]=3[NH:13]2)=[CH:18][CH:17]=1

참가 물질

7

반응물 4

HCID 8359Isatoic AnhydrideHCID 9005Trimethyl orthoformateHCID 679952474-(3-amino-2-methylphenyl)-7-bromo-3-methyl-9H-pyrido[3,4-b]indole-1-carboxamideHCID 178526924HCID 178526924, 화합물

생성물 1

HCID 679948107-bromo-3-methyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide수율 182.5%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
90 °C

실험 절차

A mixture of 4-(3-amino-2-methylphenyl)-7-bromo-3-methyl-9H-pyrido[3,4-b]indole-1-carboxamide (0.042 g, 0.103 mmol), 1H-benzo[d][1,3]oxazine-2,4-dione (0.042 g, 0.257 mmol), tris(nitrooxy)lanthanum, 6H2O (0.013 g, 0.031 mmol), and trimethoxymethane (0.337 mL, 3.08 mmol) in tetrahydrofuran (0.5 mL) in a sealed vial was heated at 90° C. for 12 h. The reaction mixture was then stirred overnight at room temperature. This reaction was repeated two additional times. The combined reaction mixtures were diluted with ethyl acetate, washed with water, washed with brine, and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by purification by flash silica gel chromatography using a mixture of ethyl acetate and hexane (20%-35%-50%-65%) afforded 7-bromo-3-methyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (0.101 g, 0.188 mmol, 59% yield) as a tan solid. LC/MS M+1=538.1 and 540.1.

후처리

  1. customThe combined reaction mixtures
  2. washwashed with water
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationConcentration under reduced pressure
  6. customfollowed by purification by flash silica gel chromatography
  7. additiona mixture of ethyl acetate and hexane (20%-35%-50%-65%)

출처 및 근거

ORD 기록
ord-a2a8878534f14a869f274022c384550e
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08685969B2

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